CFH gene rs1061170 and rs1410996 polymorphisms, and CFH serum levels association with pituitary adenoma

Abstract

Pituitary adenomas are usually benign, non-metastatic tumours. Although most PA are not malignant, up to 35% of tumours can spread to surrounding tissues. PA accounts for about 15% of all intracranial tumours and is the third most common type of central nervous system tumour after meningioma and glioma. The prevalence of PA in the general population is about 17%. While thousands of genetic variants, including single nucleotide polymorphisms (SNPs), are related to different types of cancer, the molecular mechanisms of the diseases are still not fully understood. Complement factor H (CFH) is a primary regulator of the alternative complement pathway that controls C3 activation and modulates innate immune responses. C3a stimulates anterior pituitary hormone release and activates the hypothalamic-pituitary-adrenal axis, a key regulator of inflammation. The complement molecules modulate systemic inflammatory responses through communication with the pituitary gland. Since the CFH gene is associated with inflammation, it may also be linked to cancer development and progression. The CFH gene is located on the long arm of chromosome 1 (1q32). Our aim was to determine CFH rs1061170, and rs1410996 as well as CFH serum levels in PA patients and healthy subjects and relate the obtained results to PA hormonal activity, invasiveness, and recurrence. We found that the CFH rs1061170 CC genotype and C allele were statistically significantly less frequent in the hormonal active PA group than in the control subjects (p = 0.024, p = 0.030, respectively).Moreover, CFH rs1061170 genotypes (TT, TC, CC) showed a statistically significant difference between the non-invasive PA and control group (p = 0.039). Also, the T allele of this polymorphism was statistically significantly more frequent in patients with non-invasive PA than in the control group (p = 0.034). We evaluated CFH serum level, but no statistically significant differences were found (p = 0.596). Furthermore, CFH rs1410996 showed no statistically significant differences.